Nivolumab (NIVO) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy, safety, and subgroup analyses from CheckMate 649.
Bibliographic record
Abstract
240 Background: CheckMate 649 is a randomized, global phase 3 study of 1L programmed death-1 (PD-1) inhibitor–based therapies in advanced non-HER2-positive GC/GEJC/EAC that demonstrated superior overall survival (OS) with NIVO + chemo vs chemo, leading to approvals in the US and other countries. Clinically meaningful long-term survival benefit with NIVO + chemo vs chemo was observed with 24 months (mo) of minimum follow-up in all randomized patients (pts) for both OS (HR 0.79 [95% CI 0.71–0.88]) and progression-free survival (PFS; HR 0.79 [95% CI 0.70–0.89]; Janjigian YY et al; ESMO 2021). We present expanded analyses of NIVO + chemo vs chemo with minimum follow-up of 24 mo. Methods: Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD-ligand (L)1 expression. Pts with known HER2-positive status were excluded. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses, then NIVO 240 mg Q2W), or chemo. Dual primary endpoints were OS and PFS (per blinded independent central review) in pts with PD-L1 combined positive score (CPS) ≥ 5 for NIVO + chemo vs chemo. Hierarchically tested secondary endpoints included OS in NIVO + chemo vs chemo (PD-L1 CPS ≥ 1, then all randomized). Results: Of 2031 pts, 1581 were randomized to NIVO + chemo or chemo. In all randomized pts, 41% of pts (NIVO + chemo) and 44% of pts (chemo) received subsequent therapy. Median PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death, whichever is earlier) was 12.2 (95% CI 11.3–13.5) mo with NIVO + chemo and 10.4 (95% CI 9.7–11.2) mo with chemo (HR 0.75 [95% CI 0.67–0.84]). 51% of pts (NIVO + chemo) and 43% of pts (chemo) had > 50% reduction from baseline in tumor burden, while 24% and 17% had > 80% reduction, respectively. The HR (95% CI) for OS was 0.66 (0.56–0.77) among pts with a PD-L1 CPS ≥ 10 (median OS for NIVO + chemo vs chemo: 15.0 [95% CI 13.7–16.7] vs 10.9 [95% CI 9.8–11.9] mo). OS benefit was observed with NIVO + chemo vs chemo across multiple additional subgroups, and these data will be presented. No new safety signals were identified. The majority of the treatment-related adverse events with potential immunologic etiology were grade 1 or 2 and grade 3 or 4 events were reported in ≤ 5% of pts in both treatment arms. Conclusions: NIVO + chemo continued to demonstrate clinically meaningful efficacy and an acceptable safety profile with longer follow-up, further supporting the use of NIVO + chemo as a standard 1L therapy in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".